MS is a disease of unknown cause in which a virus infection and/or immune abnormality has been implicated in the pathogenesis of demyelination. A potential clue to our understanding of MS relates to the presence of qualitative immunoglobulin (Ig) abnormalities manifest as oligoclonal Ig bands. These bands may be directed against the MS etiologic agent (recently hypothesized to be a human T-lymphotropic virus) or autoimmunogen and/or these bands may represent a "nonsense" response from immunodysregulation, unrelated to disease pathogenesis. T cell abnormalities have also been implicated in pathogenesis of MS. DA strain of Theiler's murine encephalomyelitis viruses (TMEV) causes a chronic, persistent demyelinating infection in mice, and serves as an experimental model of MS. Both the immune system and viral oligodendrocyte lysis have been implicated in the pathogenesis of demyelination. Knowledge of TMEV from a molecular point of view and the availability of an easily manipulated mouse host makes this virus system an especially valuable one to help elucidate the roles of immunity and virus lysis in demyelination. We have demonstrated qualitative Ig abnormalities in demyelinated mouse CSF using our overlay techniques. We will delineate this response with respect to time course of development, relationship to demyelinating disease, and the particular viral epitopes involved. We also plan to develop and characterize TMEV-reactive T cell lines and clones and explore their role in disease pathogenesis and demyelination. Lastly, we will use brain implants to clarify the role of the immune system in TMEV demyelination.